Core F: Induced Pluripotent Stem Cell Core Project Summary/Abstract Genome wide association studies have identified almost 30 genes that are associated with altered risk of developing late-onset Alzheimer's disease (AD). Yet, precisely how those genes impact the function of human cells to either promote or protect against the development or progression of AD remains unclear. One promising approach that is increasingly being used to examine such questions involves the use of induced pluripotent stem cells (iPSCs), which can be generated from control and AD subjects and then differentiated into the key brain cells implicated in AD. In 2013, the UCI Alzheimer's disease research center (ADRC) became the first ADRC to establish an induced Pluripotent Stem Cell (iPSC) Core. Since then, the core has generated and provided iPSC lines from AD, MCI and control subjects to researchers around the world who are using these lines to examine the impact of AD genes on human cellular function. In the current application, the iPSC Core will continue to embrace new advances in AD genetics and CRISPR gene editing to generate and distribute additional highly unique iPSC lines from UCI's three ADRC cohorts (UDS, DS, and 90+). Through five specific aims, the iPSC Core will collaborate with AD researchers worldwide (Aims 1-5), employ innovative genetic studies and genome engineering to facilitate the study of genetic AD risk factors in late- onset AD and specialized AD populations (Aims 1, 3, 4), and educate the research and lay communities about the scientific applications and implications of AD iPSCs (Aim 5).